title: Effect of single doses of methoxypolyethylene glycol-epoetin beta (CERA, Mircera™) and epoetin delta (Dynepo™) on isoelectric erythropoietin profiles and haematological parameters.
abstract: Erythropoietin (EPO) has been misused in sports for many years due to its performance-enhancing effect. In the last decade, detection of abuse has been possible with isoelectric focusing (IEF) based on the different isoform profiles of endogenous and recombinant EPO. The release of new EPOs on the market, such as the recombinant erythropoietin epoetin delta (Dynepo™) and the chemically modified EPO, CERA (Mircera™) potentially represents analytical challenges to the fight against doping. This study set out to investigate the possibility of and the time window for detecting the administration of a single dose of Dynepo™ and CERA. Our results are in agreement with earlier findings that detection of Dynepo™ is best achieved by combining IEF with SDS-PAGE. Haematological parameters were monitored for possible effects due to the long half-life (130 hours) of CERA in blood. Interestingly, although several haematological parameters were significantly changed after the injection of CERA, the endogenous EPO signal was still present in all collected samples. Due to the long half-life and the large size of the CERA molecule (about 60 kDa), it was uncertain whether CERA would be excreted into urine in detectable amounts unless urine collection was preceded by strenuous physical exercise. We find that CERA can be detected in urine without prior exercise in several, but not all, subjects. CERA is nevertheless best detected in serum with regard to both probability and length of detection, in addition to stability in matrix over time.
authors.affiliation: Norwegian Doping Control Laboratory, Oslo University Hospital, 0586 Oslo, Norway. yvette.dehnes@h-lab.no
authors.forename: Yvette
authors.initials: Y
authors.lastname: Dehnes
authors.forename: Peter
authors.initials: P
authors.lastname: Hemmersbach
mesh_terms: D004300:Doping in Sports; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004921:Erythropoietin / Q000032:analysis* / Q000097:blood / Q000652:urine; D015444:Exercise; D005260:Female; D006207:Half-Life; D006801:Humans; D007525:Isoelectric Focusing / Q000379:methods; D008297:Male; D011092:Polyethylene Glycols / Q000032:analysis*; D011994:Recombinant Proteins; D015813:Substance Abuse Detection / Q000379:methods*; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols; C516023:epoetin delta